Abstract An enduring problem for alcohol and drug abuse treatment is relapse following quit attempts. Typical animal models of relapse using operant self-administration techniques produce abstinence by withholding alcohol or drug reinforcement (i.e., extinction). Next, animals are exposed to drug, drug cues, or drug contexts to induce relapse. It is well known that drug and non-drug reinforcers interact, and treatments providing alternative non-drug reinforcers have been very successful. Unfortunately when non-drug reinforcers are discontinued, relapse is very common. More generally, some sources of relapse outside of formal treatment might be characterized as involving alternative-reinforcement loss (e.g., changes in social or vocational circumstances). Because typical animal models of relapse do not examine the role of loss of alternative non-drug reinforcement, our laboratory developed the resurgence model of relapse to alcohol seeking. In this model, self-administration is established and then suppressed via extinction while an alternative non-drug reinforcer is made available. Relapse to alcohol seeking then occurs when responding for the non-drug reinforcer is also extinguished. But, a common criticism of typical animal models of relapse, including the resurgence model, is that abstinence is achieved by extinguishing self-administration?a feature that does not correspond to the human condition. Rather, it appears that escalating negative consequences encountered as a result of continued use are a major contributor. Accordingly, increasing effort is being directed at using negative consequences to suppress alcohol and drug seeking in animal models of relapse. Such methods have been successfully applied to study relapse of alcohol seeking induced by an alcohol-associated context (i.e., renewal). The goal of this R21 Exploratory/Developmental grant is to develop a behavioral procedure for use as an animal model of relapse to alcohol seeking induced by loss of alternative non-drug reinforcement following the use of escalating negative consequences to generate alcohol abstinence. By developing a version of the resurgence procedure using escalating negative consequences to suppress alcohol seeking, the proposed research could result in a more appropriate animal model for future examinations of behavioral and neurobiological mechanisms of relapse to alcohol seeking. Finally, by using both male and female rats the project will provide important information about potential sex differences in sensitivity of alcohol seeking to escalating negative consequences and the availability and then loss of alternative non-drug reinforcement.